Indoor environment is important to a worker's health and welfare because more than half of the U.S. workforce is employed indoors. Also up to 90 percent of a typical worker's time is spent indoors. A worker's productivity is related to the indoor environment, such as the indoor air quality with an acceptable thermal comfort level. However, the widely used side-wall-supply displacement ventilation generates recirculations in the occupied zone of a large office or a workshop. These recirculations present the risk of cross infection between the workers. The floor-supply displacement ventilation could be a solution to avoid the recirculations. On the other hand, the floor-supply system could not remove a high cooling load often found in most U.S. offices and workshops, because the cold air is directly supplied to the occupied zone. This proposed research will optimize the floor-supply ventilation system to minimize the risk of cross infection among the workers in large offices and workshops with suitable air supply and exhaust locations. The investigation will also improve the design of the floor-supply displacement ventilation system for the removal of a high cooling load without a draft risk. The research will use numerical simulations through computational- fluid-dynamics (CFD) to reduce the costs. Nonetheless, detailed and high quality experimental data will be obtained in a full- scale environmental chamber, and the data will be used to validate the CFD results. The study will assess the performance of the floor-supply displacement ventilation system in terms of indoor air quality, thermal comfort, energy consumption, and first costs. The parameters to be studied include perforated degree, ventilation rate, supply air temperature, exhaust location, floor insulation, space size, furniture arrangement, etc. for five different climate regions in the U.S. The results can be used to design the ventilation systems in large offices and workshops that provide a healthy and comfortable indoor environment.